Colorectal NeoplasmsPhase 2MUTEXNCT01450319
Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favorable FcγRIIa (CD32) Genotype
A Phase 2 study testing Cetuximab in people with Colorectal Neoplasms, run by Merck KGaA, Darmstadt, Germany at 9 sites in Spain.
Trial summary
This national, multicenter, open-label phase 2 study without any control arm aims to evaluate the activity of cetuximab monotherapy in the treatment of refractory colorectal cancer in subjects with K-RAS mutated and FcγRIIa polymorphism tumors, in which there is no therapeutic alternative for treatment. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- Cetuximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 9 sitesSpain
- Study dates
- Dec 2011to Dec 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent form signed by the subject
- Age greater than or equal to (>=) 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (=<) 2
- Life expectancy of greater than (>) 2 months
- Histological confirmed colorectal cancer (CRC) with mutated K-RAS and favorable genotypes (any H in FcγRIIa-131). Selection will be done only based on Cluster of differentiation (CD)32 polymorphisms
- Epidermal growth factor receptor (EGFR) expression in his/her tumor sample
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- Stage 4 metastatic disease, with at least 1 measurable lesion according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria, documented within 28 days prior to the study inclusion
- Tumor tissue sample available for the assessment of K-RAS status and FcγRIIa (CD32) genotype
- Subject who has received at least 2 prior therapeutic lines
- Adequate bone marrow function, defined as:
- haemoglobin > 9.0 gram per deciliter (g/dL)
- platelet count >100*10^9 per liter
- absolute neutrophil count (ANC) >=1.5*10^9/Liter
- Adequate hepatic and renal function, defined as:
- Serum bilirubin =<1.5 times the upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =<2.5*ULN in absence of liver metastasis and ALT and AST =<5*ULN in the presence of liver metastasis
- Alkaline phosphatase =<2.5*ULN or =<5 in the presence of liver metastasis or =<10 in the absence of liver metastasis
- Creatinine clearance >= 50 milliliter per minute (mL/min) (according to Cockcroft and Gault formula) or serum creatinine <1.5*ULN
- Adequate recovery after recent surgery, chemotherapy or radiotherapy. Prior major surgery, chemotherapy, treatment with an investigational product or radiotherapy must have occurred at least 4 weeks before study inclusion
- Women of child-bearing potential must have a negative pregnancy test performed within 7 days prior to the study inclusion. Postmenopausal women must be amenorrheic for at least 12 months. If the risk of conception exists both male and female subjects must use effective contraception (for example, abstinence, intrauterine device (IUD), oral contraceptive, double barrier method or to be surgically sterile) since the signature of the consent form until at least 6 months after the end of treatment or end of last dose, whichever occurs first
Who cannot join
- Previous treatment with monoclonal antibodies against EGFR
- Toxicity, due to previous treatment, not resolved to Grade 1 before the subject's inclusion into the study
- Clinically relevant coronary disease or myocardial infarction, unstable angina, Grade >=2 congestive cardiac insufficiency according to New York Heart Association (NYHA) within 6 months before starting the study treatment
- Clinically significant vascular disease (for example, aortic aneurysm which requires surgery, pulmonary embolism, recent peripheral arterial thrombosis) within 12 months prior to starting the study treatment
- Evidence of uncontrolled brain metastases
- History of active neurological disease
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- History of uncontrolled seizures
- History of lung fibrosis, acute pulmonary damage or interstitial pneumonia
- Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C infection, or presence of severe, uncontrolled intercurrent infections or other severe uncontrolled concomitant diseases
- Current Grade >=2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) infection
- History of uncontrolled diabetes, uncontrolled hypertension or hepatic involvement
- Known or suspected allergy or hypersensitivity to cetuximab
- History of previous malignancy other than CRC occurring within 5 years before starting the study treatment, except for previously cured basal cell carcinoma of skin or carcinoma in situ of the cervix or urinary bladder treated more than 2 years before recruitment
- Participation in another treatment study with an investigational drug within the last 30 days
- Pregnancy or lactation
- Any medical, psychological, psychiatric or social uncontrolled problem which may interfere in the participation of the subject in the study or in the evaluation of the study results
- Psychological, familiar or geographic conditions not allowing the adequate follow-up and adherence to the study protocol
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
Spain9 sites
Research Site
A Coruña
Research Site
Asturias
Research Site
Barcelona
Research Site
Córdoba
Research Site
Madrid
Research Site
Navarra
Research Site
Santiago de Compostela
Research Site
Seville
Research Site
Valencia
About this study
Official title: Phase II Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favourable FcγR IIa (CD32) Genotype
This national, multicenter, open-label phase 2 study without any control arm aims to evaluate the activity of cetuximab monotherapy in the treatment of refractory colorectal cancer in subjects with K-RAS mutated and FcγRIIa polymorphism tumors, in which there is no therapeutic alternative for treatment. Failure of the first and second line conventional therapeutic lines was documented.
- Conditions
- Colorectal Neoplasms
- Being tested
- Cetuximab
- Keywords
- K-RAS, FcγRII/IIIa genotypes, CRC, Colorectal cancer
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux
Cetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) every 2 weeks until disease progression, death, or consent withdrawal.
| Study group | Role | What they receive |
|---|---|---|
| Cetuximab | Experimental | Not described Receives: Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Survival (OS) Time
Overall survival was defined as the time from date of informed consent signature until death.
Measured: From the date of informed consent signature until death, assessed up to 3 years
Secondary outcomes (7)
Percentage of Subjects With Disease Control Rate (DCR)
DCR was defined as those subjects achieving complete response (CR), partial response (PR) or stable disease (SD), according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v.1.1). For target lesions (TLs), CR was defined as the disappearance of all TLs; PR was defined as at least a 30 percent (%) decrease in the sum of longest diameter (SLD) of the TLs, taking as a reference the baseline (BL) SLD; Stable disease (SD) was defined as neither sufficient decrease in SLD to qualify for PR nor sufficient increase in SLD to qualify for PD; and PD was defined as at least a 20% increase in the SLD of TLs, taking as reference the smallest SLD recorded since the treatment started. For non-target lesions (NTLs), CR was defined as the disappearance of all NTLs and normalization of tumor marker levels; SD was defined as the persistence of 1 or more NTLs and/or maintenance of tumor marker levels above normal limits; and progressive disease (PD) was defined as the appearance
Measured: From the date of informed consent signature until progressive disease, assessed up to 3 years
Progression Free Survival (PFS) Time
PFS was defined as the time from informed consent signature until PD or death, whatever occurred first. Subjects who did not have disease progression or were lost to follow-up, were censored at the date of last contact, known to be alive and progression free; moreover, those subjects who started a new treatment (different from cetuximab), were censored at the date of starting the new treatment. For TLs, PD was defined at least a 20% increase in the SLD, taking as reference the smallest SLD recorded from BL or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing NTLs. Participants without second-line PD or death were censored at the date of last tumor assessment where non-progression was documented.
Measured: From the date of informed consent signature until progressive disease (PD) or death, assessed up to 3 years
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death
An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. A SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. Treatment-emergent are events between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.
Measured: From the date of enrollment up to 30 days after the last dose of study drug administration, assessed up to 3 years
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms
The antibody fragment C portion (FCy) of cetuximab interacts with Fc-gamma receptors (FCyRs) expressed by immune effector cells. Polymorphisms were described in genes coding for FCyRIIa and in FCyRIIIa. A histidine/arginine polymorphism at position 131 for FCyRIIa gene and valine ⁄ phenylalanine polymorphism at position 158 for the FCyRIIIa gene were reported to be functionally relevant in the ADCC mechanism. All subjects were analyzed and classified as carriers of every different polymorphism of FCy Receptors: for FCyRIIa (H/H, homozygous alleles with histidine and R/H, heterozygous alleles with arginine/histidine) and FCyRIIIa (V/V, homozygous alleles with valine, F/F, homozygous alleles with phenylalanine and F/V, heterozygous alleles with valine ⁄ phenylalanine) (units: subjects with every type of polymorphism) .The FCyR genotype was determined using a TaqMan Allelic Discrimination Assay.
Measured: Baseline
Overall Survival (OS) Related to Codon G13D
OS was defined as the time from informed consent signature until death. Subjects without death were censored at the last date known alive (within the study).
Measured: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal up to 3 years)
Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR)
OS was defined as the time from informed consent signature until death. Subjects without death were censored at the last date known alive (within the study).
Measured: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal assessed up to 3 years)
Beta 2-microglobulin
Measured: Baseline, Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2011 (estimated)
- Study startDec 2011
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merck KGaA, Darmstadt, Germany
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck, S.L., Spain
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Merck, S.L., Spain
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01450319
- Sponsor's protocol ID
- EMR 062202-529
- Other IDs
- 2010-023580-18
- Acronym
- MUTEX
- Status last verified
- Oct 2016
- First submitted
- 7 Oct 2011
- Last updated
- 28 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Manzanares-Martin B, Cebrian Aranda A, Del Puerto-Nevado L, Gonzalez R, Solanes S, Gomez-Espana MA, Garcia-Foncillas J, Aranda E. Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes. J Immunother Cancer. 2021 Apr;9(4):e001705. doi: 10.1136/jitc-2020-001705.
PubMed 33833048
Study at a glance
From the registry record, last updated by the sponsor on 28 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Clinical Study of Cetuximab in Refractory Colorectal Cancer With K-RAS Mutated and Favourable FcγR IIa (CD32) Genotype
- ClinicalTrials.gov ID
- NCT01450319
- Acronym / sponsor ID
- MUTEX / EMR 062202-529
- Conditions
- Colorectal Neoplasms
- Keywords
- K-RAS, FcγRII/IIIa genotypes, CRC, Colorectal cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- Merck KGaA, Darmstadt, GermanyIndustry (pharma, biotech, devices)
- Collaborators
- Merck, S.L., Spain
- Study start
- Dec 2011
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 12 Oct 2011 (estimated)
- Results
- Posted 15 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This national, multicenter, open-label phase 2 study without any control arm aims to evaluate the activity of cetuximab monotherapy in the treatment of refractory colorectal cancer in subjects with K-RAS mutated and FcγRIIa polymorphism tumors, in which there is no therapeutic alternative for treatment. Failure of the first and second line conventional therapeutic lines was documented.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cetuximab | Experimental | Drug: Cetuximab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Written informed consent form signed by the subject
- Age greater than or equal to (>=) 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (=<) 2
- Life expectancy of greater than (>) 2 months
- Histological confirmed colorectal cancer (CRC) with mutated K-RAS and favorable genotypes (any H in FcγRIIa-131). Selection will be done only based on Cluster of differentiation (CD)32 polymorphisms
Key exclusion criteria (17 listed)
- Previous treatment with monoclonal antibodies against EGFR
- Toxicity, due to previous treatment, not resolved to Grade 1 before the subject's inclusion into the study
- Clinically relevant coronary disease or myocardial infarction, unstable angina, Grade >=2 congestive cardiac insufficiency according to New York Heart Association (NYHA) within 6 months before starting the study treatment
- Clinically significant vascular disease (for example, aortic aneurysm which requires surgery, pulmonary embolism, recent peripheral arterial thrombosis) within 12 months prior to starting the study treatment
- Evidence of uncontrolled brain metastases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: ErbituxCetuximab will be administered intravenously at a dose of 500 milligram per square meter (mg/m^2) every 2 weeks until disease progression, death, or consent withdrawal. | Drug | Cetuximab |
Primary outcome
Overall Survival (OS) Time
Time frame: From the date of informed consent signature until death, assessed up to 3 years
Overall survival was defined as the time from date of informed consent signature until death.
7 secondary outcomes
Percentage of Subjects With Disease Control Rate (DCR)
Time frame: From the date of informed consent signature until progressive disease, assessed up to 3 years
Progression Free Survival (PFS) Time
Time frame: From the date of informed consent signature until progressive disease (PD) or death, assessed up to 3 years
Number of Subjects With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs Leading to Discontinuation, AEs Leading to Death
Time frame: From the date of enrollment up to 30 days after the last dose of study drug administration, assessed up to 3 years
Number of Subjects With Fcγ Receptors (FCγR) IIa/IIIa Polymorphisms
Time frame: Baseline
Overall Survival (OS) Related to Codon G13D
Time frame: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal up to 3 years)
Overall Survival (OS) Related to Killer Inhibitory Receptors 2DS4 (KIR2DS4) Functional Receptor (f/d) and Non-functional Receptor (NFR)
Time frame: From the date of informed consent signature until death, lost-to-follow-up or end of study, whatever occurred first (maximal assessed up to 3 years)
Beta 2-microglobulin
Time frame: Baseline, Week 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33833048Manzanares-Martin B, Cebrian Aranda A, Del Puerto-Nevado L, Gonzalez R, Solanes S, Gomez-Espana MA, Garcia-Foncillas J, Aranda E. Improving selection of patients with metastatic colorectal cancer to benefit from cetuximab based on KIR genotypes. J Immunother Cancer. 2021 Apr;9(4):e001705. doi: 10.1136/jitc-2020-001705.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Merck, S.L., Spain
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab in people with Colorectal Neoplasms, run by Merck KGaA, Darmstadt, Germany at 9 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Nov 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 15 Jun 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Survival (OS) Time (time frame: From the date of informed consent signature until death, assessed up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01450319, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Nov 2016.